Influence of host-recipient origin on clinical aspects of posttransplantation lymphoproliferative disorders in kidney transplantation

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) is a well-known complication of immunosuppression associated with solid organ transplantation. The donor or host origin of PTLD may influence the outcome of the disease as it has been reported that a donor origin may be associated with a better prognosis. The aim of the study was to determine the origin (recipient or donor) of 12 PTLD occurring in kidney transplant recipients and to correlate the results with clinical findings. METHODS: Origin of PTLD was determined using HLA DRB1 molecular typing, analysis of multiple short-tandem repeat microsatellite loci, and HLA class I antigen expression by immunohistochemistry. RESULTS: Combining the three techniques, we found that eight cases originated from the recipient and four cases originated from the donor. The results of the three techniques were concordant and altogether assigned the origin of the tumors. All the donor-origin PTLD were strictly localized to the kidney graft, developed after a mean time of 5 months after transplantation, and regressed after reduction of immunosuppression. In contrast, seven of the eight recipient-origin PTLD presented as multisystemic disease, occurred a mean time of 75.7 months after the transplantation, and had a worse outcome (mortality, five deaths of eight patients, 62.5%). CONCLUSIONS: These results suggest that PTLD originating from the donor arise in the first year after transplantation into the graft, and that recipient-origin PTLD develop later as an invasive disease. Because it permits simultaneously the analysis of cell morphology and tumor origin, immunohistochemistry is a more reliable technique in the case of graft tumors associated with allograft rejection. The determination of the origin of the tumors seems to be of value in the management of PTLD to predict the outcome and to adapt therapy.     

肝移植供肝修整的经验

目的：探讨肝移植供肝修整的方法与技巧。方法：回顾性分析64例原位肝移植供肝修整以及血管变异时处理的方法和技巧。结果：修整的64例供肝全部用于肝移植。发现13例存在肝动脉解剖变异，其中5例行变异肝动脉重建，动脉重建方法包括将变异动脉与脾动脉(3/5)、胃十二指肠动脉(2/5)吻合。无因供肝修整而出现的手术并发症。结论：供肝血管及胆道的正确修整可减少肝移植后并发症，是供肝修整成败的关键。     

Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children

Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients received UCBT, including 1 patient who received multiple units and 1 transplanted under nonmyeloablative condition. The time interval from UCBT to PTLD averaged 4 months (range, 2 weeks to 9 months). Patients typically presented with high-stage disease with visceral organ involvement. Histology of the PTLDs showed monomorphic morphology in 5 cases and polymorphic morphology in the remaining 2 cases. Bone marrow biopsies were performed in 3 cases and were negative for PTLD. Epstein-Barr virus (EBV) was detected in the PTLD in all 7 patients by in situ hybridization. Evidence of past EBV infection was found in the recipients, but the EBV genome was not detected in the donor cord blood samples, suggesting that donor cord blood was not the source of EBV infection. The origin of the PTLD was investigated in 5 cases. PTLD was of host origin in 2 patients who failed engraftment and of donor origin in the remaining 3 patients who had complete engraftment. Four of 5 patients with monomorphic PTLD failed to demonstrate significant responses to rituximab and/or reduction of immunosuppression and died within 1 month after diagnosis. The remaining 2 patients with polymorphic PTLD showed complete response to therapy. One patient was alive 35 months after transplant, and the other patient died of infection 6 months after transplant. It is concluded that PTLD arising after UCBT in children occurs early after transplant and represents a serious EBV-related complication. PTLD may be of donor or recipient origin depending on engraftment status. Both monomorphic and polymorphic histology may be seen, and monomorphic histology appears to predict an unfavorable prognosis.     

Hepatic flow optimization in full right split liver transplantation

Split liver transplantation for two adults offers a valuable opportunity to expand the donor pool for adult recipients.However,its application is mainly hampered by the physiological limits of these partial grafts.Small for size syndrome is a major concern during transplantation with partial graft and different techniques have been developed in living donor liver transplantation to prevent the graft dysfunction.Herein,we report the first application of synergic approaches to optimise the hepatic hemodynamic in a split liver graft for two adults. A Caucasian woman underwent liver transplantation for alcoholic cirrhosis(MELD 21)with a full right liver graft (S5-S8)without middle hepatic vein.Minor and accessory inferior hepatic veins were preserved by splitting the vena cava;V5 and V8 were anastomosed with a donor venous iliac patch.After implantation,a 16G catheter was advanced in the main portal trunk.Inflow modulation was achieved by splenic artery ligation.Intraportal infusion of PGE1 was started intraoperatively and discontinued after 5 d.Graft function was immediate withnormalization of liver test after 7 d.Nineteen months after transplantation,liver function is normal and graft volume is 110%of the recipient standard liver volume. Optimisation of the venous outflow,inflow modulation and intraportal infusion of PGE1 may represent a valuable synergic strategy to prevent the graft dysfunction and it may increase the safety of split liver graft for two adults.     

成人间活体扩大右半肝移植治疗急性肝功能衰竭

目的介绍成人间活体扩大右半肝移植治疗急性肝功能衰竭的临床经验。方法对1例42岁男性急性肝功能衰竭合并肝性脑病Ⅲ期患者行活体扩大右半肝移植治疗。其45岁姐姐为供者,CT评估供者包含肝中静脉的扩大右半肝体积为728．4cm^2（801g）,供肝／受者体重比为1．3％。供肝之肝右、中静脉整形后与受者整形后之肝右静脉行端-侧吻合;供受者门静脉、肝动脉行端．端吻合。供肝胆管整形后与受者胆总管行端-端吻合。结果供、受者手术均成功。供者术后恢复顺利,受者术后8h恢复意识,14d后丙氨酸转氨酶、总胆红素等指标首次下降至正常水平。术后16d曾出现转氨酶明显升高,给予甲泼尼龙1000mg冲击治疗后恢复正常。随访至今,供受者已健康生存8个月,均未出现胆管、肝动脉及静脉回流等并发症。结论扩大右半肝移植在技术上完全可行。能为成人患者提供足够重量的移植物,尤其对于急性肝功能衰竭患者具有重要意义,术前精确的影像学评估,熟练的肝切除和肝移植技术是确保该类手术成功的关键因素。     

Hepatic artery reconstruction in living donor liver transplantation from the microsurgeon's point of view

Microvascular surgery for the reconstruction of the hepatic artery in living donor liver transplantation is discussed from the microsurgeon's point of view. A refined operative procedure to improve the safety of the anastomosis is described. In living donor liver transplantation, the hepatic artery of the graft is short and small, the operative site is deep and mobile, and the anatomic arrangement of the graft left hepatic artery may differ from that of the recipient's dilated hepatic artery. To create a safe anastomosis under these conditions, recipient arteries that were slightly smaller than the graft artery were dissected. Without the size discrepancy, and end-to-end anastomosis could be created. Some refinements to create a good operative field made the anastomosis easy. The apparatus and techniques used in free- flap transfer facilitated a clean anastomosis. We anastomosed 44 arteries in 40 patients undergoing living donor liver transplantation using microsurgical techniques. Neither a decrease in the arterial blood flow nor hepatic artery thrombosis was noted. The refined operative procedure we describe in this report can be used to overcome the problems associated with the hepatic artery anastomosis in living donor liver transplantation. (Liver Transpl Surg 1997 Jul;3(4):388-93)     

Utility of Doppler Ultrasonography in Liver Transplantation With Celiac Axis Compression Syndrome: A Case Report

BackgroundCeliac axis compression syndrome (CACS) blocks adequate hepatic arterial flow and is a risk factor for hepatic artery thrombosis after liver transplantation. We report a case of living donor liver transplantation in a 65-year-old Brazilian male with liver cirrhosis of Child-Pugh class C and hepatocellular carcinoma caused by hepatitis C virus infection.ResultsThe patient underwent living donor liver transplantation using the graft of his 34-year-old daughter. Stenosis of the celiac artery was detected on preoperative computed tomography (CT), and CACS was suspected. Maintaining blood supply through the hepatic artery to prevent potential graft loss is essential in liver transplantation. A decrease in common hepatic artery (CHA) flow due to CACS could disturb graft blood supply or lead to hepatic artery thrombosis. In this case, we confirmed CACS through dynamic CT and used intraoperative Doppler ultrasonography (US) to plan the surgical procedure. Three types of hepatic artery reconstruction have been described in liver transplantation for CACS, namely the release of the median arcuate ligament (MAL), aorto-hepatic graft reconstructions, and reconstruction preserving the gastroduodenal artery (GDA) without MAL release. We found that clamping the GDA completely abolished hepatic inflow, but clamping the CHA did not change the hepatic inflow. Therefore, we performed arterial reconstruction without division of the GDA. The patient's postoperative course was good, with excellent hepatic artery flow, as assessed by Doppler US.ConclusionsPreoperative dynamic CT evaluation, adequate preparation of surgical procedures, and intraoperative evaluation by Doppler US is recommended in liver transplantation patients with CACS.     

Successful living donor liver transplantation for severe hepatic GVHD histologically resembling autoimmune hepatitis after bone marrow transplantation from the same sibling donor

A 30‐year‐old woman developed severe liver dysfunction 1 year after bone marrow transplantation (BMT) from an HLA‐identical sibling donor for B lymphoblastic leukemia (B‐ALL) during the tapering of cyclosporin A. The histologic picture resembled autoimmune hepatitis (AIH), although neither autoantibody nor hypergammaglobulinemia was detected. She entered hepatic coma, and underwent living donor liver transplantation from the same donor on day 421 after BMT. She is well 18 months after the procedure, showing normal liver function and hematopoiesis. AIH‐like hepatic graft‐versus‐host disease (GVHD) has not been documented. This patient is the second case of living donor liver transplantation for hepatic GVHD from the same donor.     

The use of a composite graft of iliac artery and inferior mesenteric vein in liver transplantation

Innovation may be required for satisfactory arterial reconstruction in liver transplantation, particularly when the vessels obtained from the donor are inadequate. We have used a composite graft of donor iliac artery and recipient inferior mesenteric vein (IMV) between the infrarenal aorta and donor hepatic artery. Postoperative liver function was satisfactory, with normal daily duplex ultrasound scans for the first 2 weeks. At 4 years follow up, graft function is normal, a duplex ultrasound scan shows normal arterial flow and no dilatation of the composite graft, and a magnetic resonance angiogram reveals no evidence of dilatation or thrombosis of the composite graft. This is one of the few reported cases in which a composite graft has been used to arterialize the allograft in liver transplantation. A composite graft of iliac artery and IMV provided a satisfactory outcome in this patient and may be a valuable addition to the arterial grafts available to the liver transplant surgeon.     

Usefulness of three-dimensional computed tomography in a living-donor extended right lobe liver transplantation

Although living-donor liver transplantation (LDLT) of right lobe graft is becoming a popular option for adult patients, management of venous outflow remains controversial. We report a successful extended-right lobe liver transplantation using a recipient's left portal vein as a graft from the middle hepatic vein. Preoperative three-dimensional computed tomography (3D-CT) of the donor revealed a small right hepatic vein (RHV) without inferior RHV and a large middle hepatic vein (MHV) draining segments 5 and 8. During the donor operation, right lobe graft was harvested with the MHV, preserving the drainage vein from segment 4. The donor recovered uneventfully except for mild transient hyperbilirubinemia. The recipient's condition rapidly improved, and was discharged from hospital 49 days postoperation. A 3D-CT after LDLT also clearly revealed successful vascular anastomosis. Preoperative and postoperative 3D-CT was useful for determination of the vascular anatomy and the decision about the line of transection in the donor hepatectomy, as well as for evaluation of the vascular anastomoses after transplantation. (Liver Transpl 2002;8:1076-1079.)     

猪辅助性部分肝移植模型制作及比较

目的建立猪的辅助性部分肝移植模型,观察其肝功能和术中血流动力学变化。方法 24头健康良种家猪,体质量23-30 kg,被随机分为供体(n=12)和受体(n=12)。气管插管 全麻,硫喷妥钠静脉维持。移植前切除受体肝左叶,供肝右叶作为植入肝。预实验2例行经体位转流的原位辅助性部分肝移植,对照组(5例)行简易转流下的原位辅助性部分肝移植。模型组(5例)行异位辅助性部分肝移植, 供肝被植入受体肝下间隙,供肝肝上下腔静脉与受体肝下下腔静脉端侧吻合,供肝门静脉与受体门静脉行端侧吻合,供肝肝动脉与受体脾动脉行端端吻合。供肝胆总管置管外引流。结果预实验中行体位静脉转流的原位辅助性部分肝移植的2例受体在肝上下腔静脉阻断后很快陷入血流动力学紊乱死亡。5例行简易静脉转流的原位辅助性部分肝移植的受体,2例在24 h内死亡,1例28 h,2侧超过48 h。而模型组受体 5例中有4例存活超过24 h。AST,ALT指标手术开始至术后24 h呈持续升高。模型组术中血流动力学较其他组稳定。结论该辅助性肝移植模型简明易建且具有不需静脉转流等优点,为研究辅助性部分肝移植原肝和供肝功能及血流变化提供了理想的平台。     

肝移植后供肝和宿主免疫学状态的变化

目的观察供肝免疫原性和宿主对供体抗原反应能力的动态改变。方法利用近交系LEW到WF的大鼠肝移植自发免疫耐受模型,取出不同时期的供肝,分别刺激长期生存的WF宿主,观察能否诱导出肝损害；另外对LEW→WF肝移植后不同时期的宿主,再次给予供体抗原刺激。结果(1)移植后第1、2天的同种移植肝,可激起长期生存的宿主出现暂时性肝损害(121±33、83±21),但第3天以后的则不能(28±9)。(2)给予供体同源的脾细胞刺激后,移植后7、14、28 d的宿主均未能诱导肝损害(56±17、66±11、61±35),但第56、84或112天的宿主均可被诱导出暂时性肝损害(98±25、158±43、330±82)。结论(1)肝移植后供肝的免疫原性在术后3 d基本消失。(2)移植术后1个月内宿主对供体抗原的刺激是处于低(无)反应状态的。     

Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic stem cell transplantation

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of conventional bone marrow/stem cell and solid organ transplantation. However, not much is known about PTLD following the more recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST). This study reports the findings from two cases of PTLD following NMST and compares them to the one previously reported case. The donor origin of the PTLD was determined using short tandem repeat analysis, and B- and T-cell clonalities were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total of 70 patients who have undergone NMST at our institution from 1999 to 2003. Both patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab, anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs were EBV positive (by immunohistochemistry and in situ hybridization) with diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from the previously reported case). All three PTLDs arose 6 to 7 months after NMST and were rapidly fatal. The pathology of the PTLD in all cases was donor origin, EBV positive, diffuse large B-cell lymphoma.     

Multiple Clinical Presentations of Lymphoproliferative Disorders in Pediatric Liver Transplant Recipients: A Single-Center Experience

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naïve prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.     

Jejunal Artery Can Be a Useful Option for Arterial Reconstruction in Living Donor Liver Transplantation When the Suitable Arterial Inflow Is Absent

Successful arterial reconstruction is essential for liver transplantation. In the case of inadequate arterial inflow, an arterial conduit from the aorta using artery graft or re-establishment of arterial flow through other arteries such as the splenic artery, gastroepiploic, or sigmoid artery is considered. Herein we report our experience of 27 cases of hepatic artery reconstruction using alternative methods. The most common cause of hepatic artery reconstruction requiring alternative methods was intimal dissection for which we usually used the gastroepiploic artery. Many patients had a previous operation or transarterial chemoembolization history. Among these cases, hepatic artery reconstruction using the jejunal artery was performed for 2 cases of living donor liver transplantation due to the absence of suitable alternatives. These patients have been followed up with patent hepatic arterial flow until now. Thus, the jejunal artery can be a useful option for arterial reconstruction in living donor liver transplantation when suitable arterial inflow is absent.     

A case of laryngeal posttransplantation lymphoproliferative disease

The development of posttransplant lymphoproliferative disease (PTLD) is strongly linked to infection with the Epstein-Barr virus (EBV), immunosuppression-state, the type of allograft, and EBV-seronegativity. A 18-month-old girl who had undergone living donor liver transplantation using the left lateral segment from her father was treated with tacrolimus and corticosteroid as an immunosuppressant regimen. She was readmitted 3 months after the transplant to evaluate the etiology of dyspnea and abdominal fullness as well as a decreased urine volume. She was diagnosed as an anastomotic stenosis of the hepatic vein for which she underwent balloon angioplasty. The treatment was repeated at postoperative month 5, 8, and 11. As postoperative 6 months, the result of the serological EBV-CA (IgG/IgM) was positive. In postoperative month 10, the EBV PCR serologic test become positive, and a laryngeal biopsy revealed PTLD. She was treated with acyclovir and gangyclovir as well as reduced immunosuppression. We report herein a rare case of laryngeal PTLD in a patient who had undergone living donor liver transplant with paternal allograft.     

Tumor origin and CD20 expression in posttransplant lymphoproliferative disorder occurring in solid organ transplant recipients: implications for immune-based therapy

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of transplantation for which new therapies are being explored, including cytotoxic T-cell infusion and anti-CD20 antibody. Whether the PTLD is of donor cell or recipient cell origin influences the type of cytotoxic T-cell therapy, in view of the MHC-restricted nature of the immune response. The efficacy of anti-CD20 therapy, on the other hand, depends on CD20 expression by neoplastic cells. Only limited prior data exist regarding either of these parameters. METHODS: Materials for this study were obtained in part from a Southwest Oncology Group clinical trial of solid organ transplant patients with PTLD. Tumor tissue from 21 patients (15 heart, 4 lung, and 2 kidney recipients) was evaluated for donor versus recipient origin by analyzing DNA at multiple polymorphic microsatellites. RESULTS: Twenty tumors (95%) were of recipient origin. Anatomically separate tumors from a given patient had the same origin. A single PTLD of donor origin arose in donor lung. Epstein-Barr virus (EBV), as assessed by EBER and LMP1 histochemical stains, was present in 16 of 17 tumors. CD20, evaluated immunohistochemically, was expressed diffusely in 12 of 17 tumors and focally in 3 and was undetectable in 2 tumors. CONCLUSIONS: PTLD after solid organ transplantation is frequently EBV-related and of recipient origin, implying that therapeutic EBV-specific T cells must be matched to the HLA type of the recipient, not that of the donor, in most cases of PTLD. Variable CD20 expression among tumors suggests that in some patients anti-CD20 therapy might be more effective in combination with other therapies.     

Hepatic Artery Reconstruction Using 3-in-1 Segmental Resection in Pediatric Living Donor Liver Transplantation: A Case Report and Literature Review

We report a transplant of the left lateral liver segments with 3 arteries for a pediatric recipient from a living donor. A 6-month-old female infant was diagnosed with liver cirrhosis secondary to biliary atresia and scheduled for living donor liver transplantation (LDLT; mother as donor). Left lateral hepatectomy was performed at the donor site. The dissection of the left hepatic artery (HA), which was divided immediately after its origin, showed 3 branches for segments II, III, and IV. The arteries for segment II, segment III, and segment IV were anastomosed to the recipient HA. No postoperative complications were observed. The outcome of this case demonstrates that left lateral segments with 3 arteries can be successfully used if proper surgical techniques are applied. From this experience we can recommend “3-in-1 segmental resection” in the donor can be safely done by skilled microvascular surgeons and this technique should be considered for selected cases where multiple tiny arteries supply the graft.     

Orthotopic liver transplantation from a donor with a history of schistosomiasis

The shortage of liver donors and the increasing number of patients on the waiting list for liver transplantation have led to a widening of the definition of suitable liver donors. In this case report, we describe transplantation of a liver from a 20-year-old brain-dead donor with a past history of schistosomiasis. Careful evaluation for schistosomiasis-related hepatic complications using hepatic function tests, clinical assessment for manifestations of portal hypertension, as well as abdominal ultrasound, and liver biopsy were performed. At 7 months follow-up, the recipient is doing well with normal liver function. Liver transplantation from a donor with a history of schistosomiasis is acceptable in carefully screened cases.     

Technical solutions for venous outflow reconstruction in damaged liver grafts during procurement: case reports

The incidence and clinical consequences of hepatic injuries (parenchymal, vascular, and biliary) due to surgical handling during multiorgan procurement are still underestimated. Surgical damage to liver grafts may lead to an increased mortality and graft dysfunction rate; therefore, multiorgan procurements require a high level of expertise and training. We report our experience in two cases of accidental venous outflow damage during liver procurement focusing on our repair strategies. In one case, a short suprahepatic inferior vena cava (IVC) was extended by a venous cuff obtained from a long infrahepatic IVC from the same liver graft. In the second case, we observed a complete transection of the middle hepatic vein during in situ splitting procedure. The damage was reconstructed by cadaveric iliac vein interposition. In both cases, liver transplantation was successfully performed without venous complication. An adequate surgical technique in liver procurement and venous reconstruction during living donor and domino liver transplantation are formidable tools to achieve successful liver transplantation with a damaged graft.